The length of active labor in normal pregnancies.
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Biomedical subjects
Publications and source records attributed to E A Friedman.
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Among a spectrum of renal disorders encountered in patients infected with the human immunodeficiency virus (HIV), the lesion studied most often has been the glomerular disease known as HIV-associated nephropathy. Of the other coincidental renal perturbations reported, the most significant are a heterogenous group encompassing potentially reversible acute renal failure (ARF), primarily acute tubular necrosis. While HIV-associated nephropathy may frequently be seen in asymptomatic HIV-seropositive individuals, acute tubular necrosis almost always is encountered in patients with clinical acquired immunodeficiency syndrome (AIDS). We analyzed our decade's experience in the management of 146 HIV disease patients with ARF (132 AIDS patients and 14 HIV-seropositive patients) and compared it with a contemporaneous group of 306 non-HIV subjects with ARF. All patients evaluated for ARF between January 1984 and December 1993 by the Renal Division at Kings County Hospital Center, Brooklyn, NY, were reviewed. Only those patients with ARF who reached a serum creatinine concentration of 530 mumol/L or higher were included in the analysis. Ninety-one percent of 146 HIV disease patients with ARF were less than 50 years old compared with only 33% of the 306 non-HIV subjects (P < 0.001). Septicemia was directly or indirectly responsible for 75% of patients with ARF in the AIDS group and for 39% in the non-HIV subjects (P < 0.006). Urinary tract obstruction was the cause of ARF in 54 of 306 (17%) non-HIV patients compared with none in the HIV group (P < 0.00001).(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmocologic treatment of the hyperlipidemia associated with the nephrotic syndrome with lovastatin has been previously shown to be safe and effective. However, there is no information on the effect of lovastatin treatment on plasma lipoprotein(a) [Lp(a)] levels in patients with the nephrotic syndrome. We administered lovastatin (40 to 80 mg/day) to 20 adult patients with unremitting nephrotic syndrome for 8 weeks to assess its effect on plasma Lp(a) and other plasma lipid concentrations. Apoprotein(a) (apo(a)) phenotype was determined in all patients. Patients were grouped according to their plasma Lp(a) levels. Those with elevated plasma Lp(a) (> or = 30 mg/dL) were placed in group I and those with normal Lp(a) levels (< 30 mg/dL) were placed in group II. Mean total cholesterol and LDL cholesterol were similarly and significantly reduced in groups I and II (-35.9% and -43.3%, P < 0.0005, P < 0.0005 group I, and -31.0% and -42.0%, P < 0.02, P < 0.03 group II, respectively). The median reduction in plasma Lp(a) was -32% (P < 0.003) in nephrotic patients in group I, whereas the median decline in plasma Lp(a) levels in nephrotic patients in group II was only -8.0% (P = 0.052). The overall frequency of the high molecular weight (M(r)) apo(a) phenotype S4 was 70% in nephrotic patients. There was no correlation between plasma Lp(a) and apo(a) phenotype. Treatment with lovastatin results in a favorable response in terms of total and low-density lipoprotein cholesterol lowering in patients with the nephrotic syndrome; however, plasma Lp(a) levels are uniformly and significantly reduced only in nephrotic patients with elevated baseline plasma Lp(a) concentrations. There was no correlation between plasma Lp(a) concentration and other lipid and biochemical parameters.
Erythropoietin was administered to five anemic azotemic diabetic subjects for 1 year to assess the effect of increasing red cell mass on clinical well-being and the course of renal functional decline. None of the subjects manifested worsened hypertension or cerebrovascular or cardiovascular complications despite an increase in mean hematocrit from a baseline mean of 29.6% to a mean of 39.5%. The serum creatinine concentration after 1 year of treatment with erythropoietin was 3.7 mg/dL, which was unchanged from the baseline value of 3.5 mg/dL. Plasma viscosity remained constant as red cell mass increased. Although the viscosity of whole blood rose as the hematocrit increased, it was within the range of normal blood viscosity for an equivalent hematocrit. The favorable impact of erythropoietin treatment on three diabetic subjects who had macular edema and anemia is described. One hypothesis to explain the benefit of a raised hematocrit on both diabetic nephropathy and retinopathy is that the metabolic, hormonal, and hemodynamic components of the diabetic syndrome, in concert, produce tissue and cellular hypoxia that is ameliorated in part by the greater oxygen-transporting capacity of a raised red cell mass. The pseudohypoxia of diabetes may be implicated in the pathogenesis of diabetic neuropathy, retinopathy, muscular dysfunction, and nephropathy.
Heroin-associated nephropathy (HAN), a complication of intravenous heroin abuse, was initially recognized at Kings County Hospital in Brooklyn, NY, in the early 1970s. Our recent experience indicates that after a steady incidence of new cases of HAN throughout the mid-1980s, a sharp decrease in incidence of new cases occurred starting in 1989. We sought to explore possible explanations for what amounts to disappearance of a previously prevalent disease. By means of retrospective analysis of a hospital-specific registry of new cases of end-stage renal disease (ESRD) at Kings County Hospital in Brooklyn, incidence curves from 1981 through 1993 for new cases of HAN, diabetes-induced renal disease, and human immunodeficiency virus-associated nephropathy were constructed. From hospital computer records, the number of admissions directly related to opioid abuse were extracted and charted. Unpublished surveillance records of the New York State Office of Alcoholism and Substance Abuse Services as well as reports from the New York City Department of Health, Office of AIDS Surveillance and the US Department of Justice Drug Enforcement Administration were used to determine the pattern of change in the prevalence of heroin abuse. Additionally, we used analysis of "street" heroin by the Drug Enforcement Administration to draw curves detailing drug cost and purity in New York City. There were no new cases of ESRD due to HAN for the years 1991 through 1993. The rates for new cases of ESRD due to diabetes and hypertension remained relatively constant throughout this interval.(ABSTRACT TRUNCATED AT 250 WORDS)
The superimposition of human immunodeficiency virus (HIV) infection, associated opportunistic infections, and anti-retroviral therapy further worsens the severity of anemia in patients also suffering from end-stage renal disease. A major cause of anemia in renal failure is a deficiency of erythropoietin. The causes of anemia in HIV disease include direct and indirect stem cell inhibition by the virus, increased peripheral destruction of red blood cells, and bone marrow suppression by various opportunistic infections and therapeutic drugs, particularly zidovudine. We compared the efficacy of recombinant human erythropoietin (rHuEPO) therapy in improving the anemia in HIV-infected end-stage renal disease patients (group I) with that in nondiabetic (group II) and diabetic (group III) hemodialysis patients without HIV infection. All three groups of patients were comparable in dialysis prescription and serum iron studies. Iron supplementation was prescribed to all patients, and none received blood transfusions. After 8 weeks of rHuEPO therapy (administered intravenously in a dose of 100 U/kg body weight thrice weekly), the mean increase in hematocrit was similar in all responders (5.8% increase in hematocrit in 23 of 30 HIV patients and 6.7% increase in 24 of 30 non-HIV patients). Response in hematocrit was noted in HIV patients despite the presence of opportunistic infections in 15 and zidovudine administration in 11. Seven HIV-positive patients and six non-HIV patients failed to respond to rHuEPO. Irrespective of the HIV status, the baseline serum EPO levels in patients responding to rHuEPO were significantly lower than those in nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
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We studied skin biopsies from 14 patients after 6 months to 18 years on hemodialysis (HD) to discern any effect of duration of treatment on skin and dermal capillaries. Patients selected for biopsy were without evidence of other diseases known to affect vasculature such as diabetes mellitus. Pathological changes compared with duration of HD were: capillary wall thickening, endothelial proliferation and new capillary formation, lipid content, and epidermal atrophy. Severity of morphologic changes were graded from 0 to 4+ by a pathologist who had no knowledge of HD duration. The earliest change observed was reduplication of the capillary basement membrane. Narrowing of capillary lumina due to endothelial cell proliferation and new capillary formation were noted after five years of HD; lipid droplets were noted in capillaries by five years; and epidermal atrophy by 10 years. Progressive severity of each finding was associated with length of time on HD. Neither amyloid nor Ca++ deposits were observed in any specimens. By clinical observation, easy bruisability and increased skin fragility were worse the longer the patient was on HD. Capillary occlusion inducing tissue ischemia could be a cause of the atrophic skin changes noted. However, no patient manifested dermal necrosis. While pathogenesis of the capillary changes in uremic skin is unknown, the changes have been shown to stabilize following successful kidney transplantation.
A functioning kidney transplant provides the uraemic diabetic patient a greater survival with greater rehabilitation than does either CAPD or maintenance haemodialysis. There are no reports, however, of prospective controlled studies of dialysis versus kidney transplantation in diabetic patients whose therapy was assigned randomly. For the minority ( < 10%) of diabetic ESRD patients who have insulin-dependent diabetes mellitus (IDDM), serious consideration should be devoted to performance of a combined pancreas and kidney transplant to cure diabetes. No matter which ESRD therapy has been elected, optimal rehabilitation in diabetic ESRD patients requires that effort be devoted to recognition and management of co-morbid conditions. Uraemia therapy, whether CAPD, haemodialysis or a kidney transplant should be individualized to the patient's specific medical and family circumstances. Attention to control of hypertension and hyperlipidaemia may slow the course of macrovascular disease, particularly of the coronary arteries, which threatens long-term survival of diabetic kidney recipients. Pretransplant cardiac evaluation is mandatory to identify and correct silent coronary artery disease that may be severe and life threatening. Survival is continuously improving in treating ESRD in diabetes by dialytic therapy, renal transplantation, and in IDDM, by combined pancreas and kidney transplantation. This inexorable progress in therapy reflects multiple small advances in understanding of the pathogenesis of extrarenal micro- and macrovasculopathy in an inexorable disease, coupled with safer immunosuppression.
Although remarkably successful in prolonging useful life, there is minimal probability that the majority of the world's population will benefit from contemporary therapy for irreversible renal failure because of its inordinately high cost in light of available resources. While affluent nations establish priorities for allocation of slots for maintenance dialysis of recipients of organ transplants, poor and developing countries must await the development of inexpensive, low technology treatments to substitute for absent kidney function. One attractive potential alternative to contemporary uremia therapy is the use of the intestine as a giant substitute and somewhat displaced nephron. Possible means of extracting wastes via the gut include ingestion of a mixed oral sorbent, instillation of bacterial crystallized enzymes to transform nitrogenous wastes to essential amino acids, or administration of high osmolality laxatives to promote diarrhea containing nitrogenous wastes. Any of these approaches may extract sufficient solute and water to sustain anephric life. An optimistic view of evolving uremia therapy is that within the next decade pills and purges for the poor may supplant more effective though expensive high technology approaches now encompassed in so-called modern nephrology.
Penectomy was performed to sustain life in 2 patients with insulin-dependent and non-insulin-dependent diabetes mellitus, respectively, who were undergoing maintenance hemodialysis. Both patients previously had manifested a series of serious macro- and microvascular diabetic complications. The histopathologic findings in both cases included gangrenous necrosis of penile tissue, while case 2 also evinced calcification of penile arteries. Penectomy has been reported as the result of penile malignancy, anticoagulant toxicity, self-inflicted injury, and criminal assault. Other reports document penectomies attributed to perineal infection (Fournier's syndrome) in diabetic patients with uremia. In five previously reported cases of penectomy in diabetic patients undergoing dialysis, systemwide arteriopathy was present in all. There is an association between uremia in diabetics and predisposition to an ischemic-infectious lesion of the penis that fails to respond to antimicrobial therapy.
Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (> or = 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level > or = 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm3. The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months.(ABSTRACT TRUNCATED AT 250 WORDS)
There may be cumulative 'metabolic scars' after a decade or more of long-term hemodialysis. We studied 39 patients who have been on maintenance hemodialysis for 10-24 years to determine their functional status and pathobiology. The 39 long-term (> or = 10 years) patients were compared with a control cohort of 37 age-, gender-, race-, and renal-diagnosis-matched patients on hemodialysis for < or = 3 years. The functional status was measured using a modified Karnofsky scale, and the employment status was noted as well. Details of hospitalizations and intercurrent infections requiring outpatient oral or intravenous antibiotic therapy during the preceding year were obtained. Comorbid medical conditions were documented, and basic laboratory tests were performed. The mean age of the long-term patients was 51.8 +/- (SE) 1.9 years, and the mean age of the control group was 51.5 +/- 2.4 years (p = 0.92). Three times weekly hemodialysis prescriptions were similar in both groups (long-term: 3.5 +/- 0.02 h, control: 3.4 +/- 0.02 h; p = 0.27). The mean modified Karnofsky scores were equivalent in both groups. The rate of hospitalization during the preceding year was higher among the long-term patients (0.92 +/- 0.19/patient year) than in the control patients (0.51 +/- 0.15/patient year; p = 0.09). The long-term patients had more intercurrent infections (1.23 +/- 0.21) than the controls (0.68 +/- 0.16; p = 0.04). (ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND: Recognition of advanced abdominal pregnancy and care of the patient afflicted with it may present formidable challenges. Aside from the difficulty of diagnosing the problem and thereby delaying necessary intervention, management can be difficult at best, even when the condition is relatively uncomplicated. When it is compounded by a life-threatening complication, such as uncontrollable hemorrhage, it challenges the skills of the most experienced obstetrician and the resources of the best-equipped facility and its personnel. CASE: Partial placental separation was encountered at surgery; it progressed intraoperatively despite the care taken to avoid disturbing the placental implantation site. Severe hemorrhage was controlled by a combination of aortic compression, packing and use of large "liver" sutures incorporating the uterine wall for tamponade of the principal placental implantation site, on the mesentery. CONCLUSION: It is important to be prepared to deal with the complication of intense intraabdominal bleeding in the course of intraoperative management of abdominal pregnancy.